6b- Lymphocytosis/lymphoid leukemia

Question 1

What is CLL/SLL?

Answer 1

• CLL/SLL= chronic lymphocytic leukemia/small lymphocytic lymphoma
• Most common leukemia in the western world

Question 2

What are the demographics and presentation of CLL/SLL?

Answer 2

• Mean age at diagnosis= 65 yo
• Symptoms:
  
  • most patients asymptomatic (indolent disease)
  • worked up due to lymphocytosis
  • may have lymphadenopathy

Question 3

What is Richter syndrome?

Answer 3

The transformation of an indolent CLL/SLL to aggressive B cell lymphoma (happens in 2-8% of cases)

Question 4

What are some histological findings for CLL/SLL leukemia?

Answer 4

• Leukemia= blood and BM involvement (“wet”)
  
  • Knotting lymphocyte chromatin
  • Smudge cells (not diagnostic for CLL/SLL but commonly seen)
  • BM lesions

Question 5

What are some histological findings for CLL/SLL lymphoma?

Answer 5

• Tissue based (lymph nodes, spleen, MALT)
• Proliferation centers (don’t worry about identifying on exam)
  
  • pale, ill-defined nodules
  • prolymphocytes admixed with small lymphocytes with pale cytoplasm (“Soccer ball cells”)

Question 6

How do you differentiate types of Small B cell leukemia/lymphoma?

Answer 6

• CD5
• CD23
• CD10

Question 7

Describe some good (3) and bad (4) prognostic factors for CLL/SLL

Answer 7

• Good
  
  • low Rai stage
  • mutated Ig Heavy Variable (IGHV) gene
  • deletion 13q
• Bad
  
  • high Rai stage
  • unmutated IGHV gene
  • CD38/ZAP-70 expression
  • deletion 11q, 17p

Question 8

Describe Rai staging system

Answer 8

For staging CLL/SLL

(better prognosis the lower the stage)

Question 9

What are the indications to treat CLL/SLL?

Answer 9

• treat Rai stages III/IV
• labs
  
  • rapid lymphocyte doubling time (<6 months)
  • Hgb < 10g/dL
  • Platelets < 100k/uL
• clinical
  
  • autoimmune anemia/thrombocytopenia
  • richter transformation
  • enlarging symptomatic (or bothersome) lymph nodes

Question 10

What are the treatment options for CLL/SLL?

Answer 10

• chemotherapy
• targeted cell therapy
  
  • BCL2 inhibitor
  • PI3 kinase
  • BTK inhibitor: Ibrutinib
• immunotherapy
  
  • CD20 antibodies
• cellular therapy
  
  • stem cell (BM) transplant
  • CAR-T cells

Question 11

What is FCR treatment?

Answer 11

• For CLL/SLL
• Fludarabine + Cyclophosphamide + Rituximab
• Combination of drugs for complicated course of treatment
• Works better/worse depending on cytogenetics:
  
  • Better for trisomy 12, 13q and 11q deletion
  • Worse for 17p deletion

Question 12

What is ibrutinib?

Answer 12

• Oral irreversible BTK inhibitor
  
  • inhibits proliferation and survival
  • inhibits adhesion
  • modulates chemotaxes and trafficking
• Effectiveness NOT determined by cytogenetics
• NOT a cure (need to be on a daily pill for life)

Question 13

What is venetoclax?

Answer 13

• BCL2 inhibitor
  
  • pushes cells to commit suicide (normally BCL2 inhibits apoptotic pathway)
• Better outcomes than chemotherapy

Question 14

What disorders can present with atypical lymphocytes with OR without lymphocytosis?

Answer 14

• CLL/SLL (usually presents with lymphocytosis)
• Leukemic lymphoma (follicular, mantle, etc)
• Hairy cell leukemia
• Adult T cell leukemia/lymphoma
• Sezary syndrome

Question 15

What disease does this blood smear likely represent?

Answer 15

Hairy cell leukemia

Question 16

Describe hairy cell leukemia

Answer 16

• 40-60 yo males
• splenomegaly (red pulp infiltration)
• pancytopenia
• “hairy” lymphocytes +/- lymphocytosis
• TRAP + cells
• BM fibrosis leading to “dry” spinal tap
• Flow cytometry -> bright CD11c and CD22 expression
• indolent disease

Question 17

What disease does this blood smear likely represent?

Answer 17

Sezary syndrome (lymphocytes with “cerebriform” nuclei)

Question 18

Describe Sezary syndrome

Answer 18

• CD4 T cell neoplasm
• triad: erythroderma, generalized lymphadenopathy, circulating sezary cells (cerebriform nuclei)
• related to mycosis fungoides
• may transform into aggressive T cell tumor

Question 19

What is mycosis fungoides?

Answer 19

Sezary cell infiltration of the epidermis

Question 20

What disease does this blood smear likely represent?

Answer 20

Adult T cell leukemia/lymphoma (“flower” cells)

Question 21

Describe adult T cell leukemia/lymphoma

Answer 21

• CD4 T cell neoplasm
• associated with retroviral infection (HTLV-1)
• more common in Japan, Caribbean, and Africa
• “flower cell” with lymphocytosis
• hypercalcemia
• aggressive clinical course

Question 22

What disease does this blood smear likely represent?

Answer 22

Large granular lymphocytic leukemia

Question 23

Describe large granular lymphocytic leukemia

Answer 23

• lymphoporliferative disorder of CD8 T cells
• indolent
• usually presents with neutropenia, anemia, and splenomegaly
• associated with autoimmune disease (esp rheumatoid arthritis)